- Function
- Transporter — p=1.00. From sequence alone Astra assigns transmembrane-transporter activity (GO, p=0.94), confirming the SLC38/SNAT-family annotation for a member whose substrate is unknown.
- Topology
- Multi-pass plasma-membrane protein (p=1.00); ~ten transmembrane helices, the classic amino-acid-transporter architecture.
- Substrate Pocket
- High-confidence hypothesis (0.80). A residue-level central cavity lined by five different TM helices — the translocation site a docking or mutagenesis campaign needs to start deorphaning.
- Modifications
- Predicted N-glycosylation (N44, N275) on the extracellular loops — consistent with a plasma-membrane transporter.
- Clean Signal
- No amyloidogenic segments predicted.
Model-reported confidence for the headline calls (amber = the load-bearing prediction the rest of the profile builds on). These are model-estimated probabilities that rank and gate each call — not calibrated rates of experimental success.
The Gap
Why This Target Is Still Dark
The solute-carrier (SLC) superfamily is the largest group of human membrane transporters, and roughly a third of it remains functionally orphan — no known substrate. SLC38A11 is one of these: UniProt calls it a putative sodium-coupled neutral amino-acid transporter, a member of the SLC38 (SNAT) family whose better-studied relatives SLC38A1/A2/A5 are validated cancer and CNS glutamine-cycle transporters. But SLC38A11 itself has no confirmed substrate, a thin literature (IDG Tdark), and no experimental structure in the PDB.
That combination — a disease-relevant family with an uncharacterised member — is exactly where prediction earns its keep: everything below is computed from the canonical 406-residue sequence and derived structural predictions, with no experimental SLC38A11 structure used as input.
Architecture & Topology
How the Sequence Is Organised
| Element | Residues | Note |
|---|---|---|
| N-terminus / extracellular loops | N44, N275 | N-glycosylation sites on the extracellular side; consistent with a plasma-membrane transporter. |
| Transmembrane core | ~10 helices | About ten transmembrane helices; ~47% of the chain membrane-embedded — the classic amino-acid-transporter architecture. |
| Substrate-cavity helices | TM2, TM4/5, TM7, TM8 | Five different TM helices sit far apart in sequence but converge in space to line the predicted central substrate cavity. |
The Predicted Pocket
The Predicted Substrate Cavity
A genuine orphan cavity — no known substrate or binder. The residues above are the first, testable hypothesis for what SLC38A11 might carry; as a control, the same pocket detection recovers known substrate/ligand sites on transporters whose structures are solved.
Site: Central cavity lined by five transmembrane helices (TM2, TM4/5, TM7, TM8)
Post-Translational & Structural Features
Specific, Testable Residues
- Extracellular N-glycosylation (N44, N275). The expected surface modification for a multi-pass plasma-membrane transporter — and a handle for trafficking / surface-expression assays.
- Predicted disulfide / loop features. Consistent with a folded, membrane-inserted transporter rather than a disordered protein (~10% disorder overall).
- No amyloid signal. A clean, foldable transporter fold.
Recommended Experimental Follow-Up
An Orphan Sequence, Turned Into a Ranked Plan
Each prediction is paired with the experiment that would test it and the readout to watch for.
| Prediction | Experiment | Readout |
|---|---|---|
| Transporter function | Radiolabel amino-acid uptake panel (Na+-dependent) | Confirm transport + a substrate class |
| Substrate cavity residues | Alanine scan at the cavity + docking | Loss/shift of transport; substrate hypothesis |
| ~ten-TM topology | Surface-labelling / glycosylation-mapping | Confirmed topology and orientation |
| N-glycosylation (N44, N275) | N→Q mutants | Trafficking / surface-expression change |
| Family relationship (SNAT) | Compare cavity residues to SLC38A1/A2/A5 | Predicted substrate similarity / difference |
Scope & Limitations
What This Is — and Isn't
- Prediction, not experiment. These are computational hypotheses to prioritise experiments — not a substitute for a structure or an assay. No result here has been validated in the wet lab.
- The cavity is predicted; the substrate is not named. For a genuine orphan the honest output is a residue-level cavity hypothesis, not a substrate assignment.
- Biology caveats. SLC38A11's substrate and physiological role are unknown; family-level disease relevance (SLC38A1/A2/A5) does not by itself establish a role for SLC38A11. Treat function as an open question.
All predictions were generated with Orbion's Astra suite from the canonical SLC38A11 sequence (UniProt Q08AI6), using AlphaFold-derived structural features. Reported values are model outputs; model internals are out of scope.
References
- [1]UniProt Consortium. UniProtKB entry Q08AI6 (SLC38A11, human). uniprot.org.
- [2]Pharos / Illuminating the Druggable Genome. SLC38A11 target record — Tdark. pharos.nih.gov/targets/Q08AI6.
- [3]Bröer S. The SLC38 family of sodium-amino acid co-transporters. Pflügers Arch. 466(1), 155–172 (2014). https://doi.org/10.1007/s00424-013-1393-y
- [4]Mackenzie B., Erickson J.D. Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflügers Arch. 447(5), 784–795 (2004). https://doi.org/10.1007/s00424-003-1117-9
- [5]Pizzagalli M.D., Bensimon A., Superti-Furga G. A guide to plasma membrane solute carrier proteins. FEBS J. 288(9), 2784–2835 (2021). https://doi.org/10.1111/febs.15531